Preparation and optimization of nilotinib self-micro-emulsifying drug delivery systems to enhance oral bioavailability

Zakkula, Ashok; Gabani, Bhavesh Babulal; Jairam, Ravi Kumar; Kiran, Vinay; Todmal, Umesh; Mullangi, Ramesh

doi:10.1080/03639045.2020.1730398

Cited by 17 publications

(5 citation statements)

References 15 publications

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“…The emulsion regions can be identified by plotting pseudo-ternary phase diagrams. The area was where oil, emulsifier, and co-emulsifier are mixed in a certain ratio to form a uniform and transparent emulsion ( 40 ). In this study, the fixed emulsifier and co-emulsifier were kolliphor ELP and isopropanol when the oil phase was examined by pseudo-ternary phase diagram.…”

Section: Resultsmentioning

confidence: 99%

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

et al. 2021

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The aim of this article was to design a self-emulsifying drug delivery system (SEDDS) of loaded cepharanthine (CEP) to improve the oral bioavailability in rats. Based on the solubility determination and pseudo-ternary phase diagram, isopropyl palmitate (IPP) was chosen as the oil phase. Meanwhile, Cremophor RH40 and Macrogol 200 (PEG 200) were chosen as the emulsifier and co-emulsifier, respectively. This prescription was further optimized by using central composite design of response surface methodology. The optimized condition was CEP:IPP:Cremophor RH40:PEG 200=3.6:30.0:55.3:11.1 in mass ratio with maximum drug loading (36.21 mg/mL) and the minimum particle size (36.70 nm). The constructed CEP-SEDDS was characterized by dynamic light scattering, transmission electron microscopy, in vitro release and stability studies. The dissolution level of CEP-SEDDS was nearly 100% after 30 min in phosphate-buffered saline (PBS, pH 6.8) which was higher than that of the pure CEP (approximately 20%). In addition, in vivo pharmacokinetic study in rats showed that CEP-SEDDS dramatically improved bioavailability compared with active pharmaceutical ingredient (API) (the relative bioavailability was 203.46%). In this study, CEP-SEDDS was successfully prepared to enhance the oral bioavailability which might facilitate to increase its better clinical application. Graphical abstract

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Section: Resultsmentioning

confidence: 99%

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

et al. 2021

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“…Next, these mixtures were stirred magnetically at 37 °C prior to dropwise addition to 100 mL ultrapure water (UPW, Millipore Corporation, Bedford, MA, USA). The performance of the formulation was assessed visually through the following classification system: 14 (I) Nanoemulsion, the transparent appearance or slightly blue. (II) A slightly opaque emulsion with a bluish appearance.…”

Section: Methodsmentioning

confidence: 99%

Enhanced oral bioavailability and anti‐hyperuricemic activity of liquiritin via a self‐nanoemulsifying drug delivery system

et al. 2021

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BACKGROUND This study focused on the development of a self‐nanoemulsifying drug delivery system (SNEDDS) to improve, potentially, the solubility and oral bioavailability of liquiritin (LQ). METHODS The solubility of LQ in different types of excipient, namely oils (OLs), emulsifiers (EMs), and co‐emulsifiers (CO‐EMs), was evaluated, and a pseudo‐ternary phase diagram (PTPD) and the formulation optimization were established. The prepared self‐nanoemulsifying drug delivery system of liquiritin (LQ‐SNEDDS) was assessed using droplet size (DS), zeta potential (ZP), polydispersity index (PDI), droplet morphology, drug release in vitro, and oral bioavailability. RESULTS After the dilution of the LQ‐SNEDDS, a transparent nanoemulsion was obtained with an acceptable DS (24.70 ± 0.73 nm), ZP (−18.69 ± 1.44 mV), and PDI (0.122 ± 0.006). The LQ‐SNEDDS that was developed had a better release rate in vitro than the free LQ suspension. Pharmacokinetic evaluation showed that the relative oral bioavailability of LQ‐SNEDDS was increased by 5.53 times, and LQ‐SNEDDS exhibited a delayed half life and longer retention time in comparison with those of free LQ. Similarly, LQ‐SNEDDS had a better urate lowering effect and provided better organ protection than free LQ at the same dose (P < 0.05). CONCLUSIONS The incorporation of LQ into SNEDDS could serve as a promising approach to improve the solubility, oral bioavailability, and anti‐hyperuricemic effect of LQ. © 2021 Society of Chemical Industry.

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“…The C max of PTX-S-S-LA SMEDDS group (93.12 ng/mL) was significantly higher than that of PTX SMEDDS group (31.2 ng/mL) and PTX solution group (48.4 ng/mL) after oral administration. The orally administered SMEDDS formulation showed a slow rate of absorption, and the release of PTX was sustained compared with the PTX solution group. Due to the decreased absorption rate of PTX from SMEDDS formulation, the T max of PTX SMEDDS was delayed and the C max was reduced.…”

Section: Resultsmentioning

confidence: 91%

Incorporating a Lipophilic Disulfide-Bridged Linoleic Prodrug into a Self-Microemulsifying Drug Delivery System to Facilitate Oral Absorption of Paclitaxel

et al. 2022

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The oral absorption of paclitaxel (PTX) is restricted by poor solubility in the gastrointestinal tract (GIT), low permeability, and high first-pass metabolism. Lipid carriers, such as a self-microemulsifying drug delivery system (SMEDDS), have been deemed as promising vehicles for promoting oral delivery of PTX. Herein, a lipophilic disulfide-bridged linoleic prodrug (PTX-S-S-LA) was synthesized and efficiently incorporated into SMEDDS to facilitate the oral absorption of PTX. This study mainly aims to evaluate the usefulness of the disulfide-bridged linoleic prodrug incorporated with SMEDDS and provides a new strategy for efficient oral delivery of PTX. The prodrug SMEDDS showed a markedly higher drug loading efficiency (3fold) compared to that of parent PTX. PTX-S-S-LA SMEDDS significantly increased the drug partition (about 1.9-fold) in the intestinal micellar aqueous phase compared to PTX in the in vitro lipolysis study. Additionally, the gastrointestinal (GI) biodistribution study demonstrated that SMEDDS could enhance the GI biological adhesion and go through the lymphatic system to transport. Moreover, it was found that the reduction-sensitive prodrug (PTX-S-S-LA) has good stability in the GIT, leading to an improved antitumor efficiency without significant GI toxicity. Overall, the PTXlinoleic prodrug (PTX-S-S-LA) in combination with SMEDDS provides a promising way to enable effective oral delivery of PTX.

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Preparation and optimization of nilotinib self-micro-emulsifying drug delivery systems to enhance oral bioavailability

Cited by 17 publications

References 15 publications

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

Preparation and Evaluation of Self-emulsifying Drug Delivery System (SEDDS) of Cepharanthine

Enhanced oral bioavailability and anti‐hyperuricemic activity of liquiritin via a self‐nanoemulsifying drug delivery system

Incorporating a Lipophilic Disulfide-Bridged Linoleic Prodrug into a Self-Microemulsifying Drug Delivery System to Facilitate Oral Absorption of Paclitaxel

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